Involvement of CGRP receptors in retinal spreading depression

Abstract

Background: Cortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine with aura and is regarded as the underlying cause of migraine. Calcitonin-gene related peptide (CGRP) receptors play a crucial role in mediating the magnitude of CSD in rat cortical slice. This study aimed to examine whether CGRP receptors are involved in retinal spreading depression (RSD) in chicks.

Methods: Western blot was used for detection of calcitonin-receptor like receptor (CALCRL) and intrinsic optical imaging was used for pharmacological investigation.

Results: We found that the key component of CGRP receptor, CALCRL, is expressed in the chick retina. Using an in vitro migraine RSD model, we demonstrated that BIBN4096, a potent antagonist for CGRP receptors, markedly reduced the magnitude of RSD induced by K(+), but also the propagation rate.

Conclusions: The data suggest that CGRP receptors mediate RSD propagation involving neuronal mechanism and approve that RSD is an efficient in vitro approach for assessing anti-migraine drugs targeting CGRP receptors.

Keywords: BIBN4096; Calcitonin-gene related peptide receptor; Chick retina; Migraine; Retinal spreading depression.